. PROJECT SUMMARY (See instructions); The Drug Discovery and Structural Biology Core (DDSB) is a new shared resource that supports the identification and development of small molecule and macromolecular therapeutics for the basic, translational and clinical scientists at COHCCC. The overarching goal of DDSB is to provide the necessary scientific resources to assist In chemical biology studies and development of molecularly-based therapeutics. DDSB comprises several scientific disciplines that include medicinal chemistry, biopolymer synthesis, high throughput screening, and X-ray crystallography. Rather than have separate cores for each, these disciplines are consolidated under one unit for maximum efficiency in drug development. This has resulted in unique shared resource that works in concert to achieve the basic and translational research goals of the Cancer Center. Specific areas of expertise and services provided include: synthetic organic chemistry, custom synthesis of specialized RNA and DNA, assay development, high-throughput screening, protein production, biophysical characterization and structural biology. The amalgamation of these services provides a seamless drug discovery pipeline for development of novel molecular targets. The DDSB core is focused yet flexible to allow Cancer Center members to use any one of these services individually or in combination. An additional significant component of the DDSB is to consult with Pis, develop reagents and assays, and obtain preliminary results to support the application of externally funded proposals by Cancer Center members. For example, the DDSB has developed COH29, a novel small-molecule inhibitor that is a dual PARP/rlbonucleotide reductase antagonist and has promising activity against BRCA1 deficient cancers. This work has led to new ROI funding and our first drug candidate for GMP synthesis and clinical trials developed completely in-house. Collectively, the DDSB serves as a scientific and intellectual hub for Integrating diverse disciplines such as molecular modeling, bioinformatics, and pharmacology in a transdisciplinary approach towards the development of new agents for the treatment of cancer. The DDSB Is unique in this capacity as it provides a complete program of scientific services and coordination of efforts for drug discovery in an academic setting. Thus, Pis can leverage the DDSB core for pursuing avenues of research not previously available at one site in an academic center, thereby accelerating the development of chemical biology probes and molecularly-targeted therapies for clinic trials at COHCCC.